Reactions of (RP)- and (SP)-tert-butylphenylphosphinobromidates and tert-butylphenylthionophosphinochloridates with heteroatom nucleophiles; preparation of P-chiral binol phosphinates and related compounds

Article abstract of DOI:10.1016/S0040-4039(00)01950-X

Reaction of (R_P)- and (S_P)-tert-butylphenylphosphinobromidates and tert-butylphenylthionophosphinochloridates with metallated phenol and BINOL alkoxides, thioalkoxides, amides and enolates leading with clean inversion at phosphorus t

Full text of DOI:10.1016/S0040-4039(00)01950-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 453–456
Reactions of (RP)- and (SP)-tert-butylphenylphosphinobromidates
and tert-butylphenylthionophosphinochloridates with heteroatom
nucleophiles; preparation of P-chiral binol phosphinates and
related compounds
Tin-Lok Au-Yeung, Ka-Yee Chan, Wai-Kuen Chan, Richard K. Haynes,* Ian D. Williams and
Lam Lung Yeung
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong
Received 29 August 2000; revised 23 October 2000; accepted 2 November 2000
Abstract—Reaction of (RP)- and (SP)-tert-butylphenylphosphinobromidates and tert-butylphenylthionophosphinochloridates
with metallated phenol and BINOL alkoxides, thioalkoxides, amides and enolates leading with clean inversion at phosphorus to
phosphinates, phosphinothiolates and phosphinoamidates, and the corresponding thionophosphorus compounds are described.
© 2001 Elsevier Science Ltd. All rights reserved.
Phosphinobromidates (RP)-3 and (SP)-3 have been pre-
pared previously (Scheme 1).4,5 Whilst thionophosphi-
nochloridate (RP)-4 is also known,6 use of thionyl
chloride on (RP)-2 in CH2Cl2 to give (RP)-4 in 30% yield
(Scheme 1) with ee >99% as analysed by HPLC (Chi-
ralcel OJ, hexane) represents a far simpler method for
its preparation. Absolute configuration of (RP)-4 was
confirmed by X-ray diffractometry.7 The yield of (RP)-4
becomes near quantitative when oxalyl chloride in
CH2Cl2 is used, albeit with a slight decline in optical
purity (96% ee). A single recrystallization of (RP)-4
gives a product of over 98% ee. Reactions of the
bromidates 3 with heteroatom nucleophiles are sum-
marised in Table 1. For entries 1–9, a solution of the
alcohol, thiol or amine (1.0 mmol) in THF (5 mL) was
treated with sodium hydride (1.0 equiv.) at 0°C. After
5–10 min of stirring, the sodiated nucleophile was
treated with a solution of racemic, (RP)- or (SP)-3 (1.0
Synthesis of P-chiral tertiary phosphines and phosphine
oxides relies on stereoselective substitution of O- or
S-alkyl groups at phosphorus by organometallic
reagents.1 Less attention has been focused on the single
displacement at a strictly P-chiral centre by nucle-
ophiles other than carbanions to give heteroatom PV
substituted compounds. Enantiopure tert-butyl-
phenylphosphine oxides (RP)-1 and (SP)-1 are easily
prepared from the readily resolved phosphinothioic
acids (RP)-2 and (SP)-2, and react as nucleophiles with
alkylating agents and carbonyl compounds to provide
functionalised tertiary phosphine oxides.2,3 In order to
expand the utility of these reagents, we have examined
the reactivity of the derived PV electrophiles, namely the
phosphinobromidate 3 and thionophosphinochloridate
4 with various heteroatom nucleophiles, with the pur-
pose of assessing the ligating properties of the products
in asymmetric catalysis.
Scheme 1.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01950-X

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T.-L. Au-Yeung et al. / Tetrahedron Letters 42 (2001) 453–456
or 2.0 equiv.) in THF (5 mL) at the same temperature.
The reaction time ranged from 5 min for pyrrole (en-
try 9) to 12 h for BINOL (entries 3–6). For entries 10
and 11, the ketone (1.2 mmol) in THF (5 mL) was
treated with LDA (1.2 mmol) at 0°C and stirred for
15 min followed by the dropwise addition of the bro-
midate (1.0 mmol) in THF (5 ml) at –78 °C, and
workup after 1 h.
Table 1. Reaction of bromidates Rac-3, (RP)-3 and (SP)-3 with heteroatom nucleophiles

T.-L. Au-Yeung et al. / Tetrahedron Letters 42 (2001) 453–456
455
Table 2. Reaction of thionophosphinochloridate (RP)-4 with heteroatom nucleophiles
The products had enantiomeric excesses (ee) ]98.5%
as assayed by 1H NMR spectroscopy with (Sp)-tert-
butylphosphinothioic acid.2 The exception was in the
product from pyrrole (entry 9), for which the ee was
78%. Absolute configuration at phosphorus in products
7, 10 and 13 (entries 3, 6 and 8) as determined by X-ray
crystallography is inverted with respect to that in bro-
midate 3.7 Racemic BINOL and (Sp)-3 gave phosphi-
nates 8 and 9, easily separated by chromatography
(entry 5); the former was prepared from (R)-BINOL
and (Sp)-3 (entry 4). The reaction represents an easy
way to resolve racemic BINOL, as the product phos-
phinates may be hydrolysed. Related, although less
straightforward, methods for resolution have been de-
scribed elsewhere.8 On the other hand, (R)-BINOL with
racemic bromidate 3 afforded phosphinates 8, 10 and
11 (entry 6). While phosphinate 8 was easily isolated as
a result of its different polarity, 10 and 11 could not be
separated by chromatography or fractional crystallisa-
tion; however, a single crystal of 10 was obtainable
from the mixture for crystallography. The 31P NMR
spectrum of the mixture has a signal due to 10 at l
49.4, and two other signals of equal intensity at l 48.4
and 50.1 ppm, due to the RP- and SP-centres in the
(RP,R,SP)-isomer 11. The compounds, in possessing
axial chirality and two chiral phosphorus atoms, are
representative of a compound class of which very few
other examples are known.9 Enolates react with bromi-
date 3 exclusively through the oxygen atom (entries 10
and 11).
yields. X-Ray crystallographic determination of the
structures of 18 and 19 (entries 2 and 3)7 indicate that
displacement of chloride from (R)-4 proceeds with in-
version of configuration. As in the previous case involv-
ing the reaction of pyrrole with bromidate (entry 9,
Table 1), displacement of chloride in (R)-4 is not
completely stereoselective (entry 5).
In summary, the PV P-chiral electrophilic halidates 3
and 4 react with O-, S-, and N-nucleophiles with inver-
sion of configuration at phosphorus to provide phos-
phinates, phosphinothiolates, phosphinamides and the
corresponding thionophosphorus compounds in good
to excellent yields. One application of these products is
described in the following communication.
Acknowledgements
We thank the Hong Kong Research Grants Council
(Grants HKUST 706/96P and HKUST 6170/97P) for
generous support of this work. Preparation of the
BINOL bisphosphinates was carried out under the
RGC Central Allocation Grant (Grant ‘Open Labora-
tory for Asymmetric Synthesis’; E-RB03).
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